Levels of apoptosis factors in mitochondria of brain cortex cells in female С57ВL/6 mice in dynamics of B16/F10 melanoma growth combined with comorbidity

Abstract

Purpose of the study. To analyze the apoptosis indicators in mitochondria of brain cortex cells in female С57ВL/6 mice in the dynamics of B16/F10 melanoma growth alone and in combination with comorbidity, i.e. chronic neurogenic pain.Materials and methods. Female С57ВL/6 mice (n = 168) were used in the experiment. Groups accounted: intact group (n = 21); control group (n = 21) with a model of chronic neurogenic pain (CNP); comparison group (n = 63) with B16/F10 melanoma transplanted subcutaneously; main group (CNP + B16/F10) (n = 63). Levels of cytochrome C (ng/mg protein), caspase 9 (ng/mg protein), Bcl‑2 (ng/mg protein), AIF (ng/mg protein), calcium (Ca 2+) (mMol/g protein) were measured by ELISA in mitochondrial samples. Statistical analysis was performed using the Statistica 10.0 program.Results. In a week of the tumor growth in presence of comorbidity, i.e. CNP, levels of calcium in murine brain cortex mitochondria were 1.4 times higher (p < 0.05) than in the comparison group at the same time; in 2 weeks the levels declined by 80.1 times and after 3 weeks declined by 37.7 times. Compared to the values in the comparison group AIF levels in animals with CNP+B16/F10 were lower by 25 and 1.8 times (p < 0.05) at weeks 1 and 3, respectively. Higher levels of Вcl‑2 in the group with CNP + B16/F10 were registered at weeks 2 and 3 by 2 and 1.4 times (p < 0.05), respectively. Levels of cytochrome C were decreased in animals with CNP+B16/F10 at weeks 1–3 by 3.2, 1.5 (p < 0.05) and 2.8 times, respectively. Caspase 9 in CNP+B16/F10 after 3 weeks exceeded the values in the comparison group by 2.6 times.Conclusions. Combination of CNP and melanoma at an early stage in the animal body promotes the accumulation of calcium and suppression of AIF and cytochrome C in mitochondria of the brain cortex. By the terminal stage of tumor growth in presence of comorbidity (CNP), suppression of most units of the respiratory chain of mitochondria of brain cortex cells is formed.